Tumorigenesis involveds aseries of cellular changes that progressively transform normal cell into malignant cancer cells. The goal of this program of basic research is to understand in molecular detail the cellular changes that lead to tumorigenesis. The cellular changes that we address include: (I) changes in the regulation of DNA replication that lead to cell proliferation; (ii) induction of telomere synthesis for maintenance of chromosome stability in replicating cells; (iii) sensitization and subsequent resistnce of cancer cells to programmed cell death or apoptosis in response to oncogenes; and (iv) changes in transcriptional and post- transcriptional regulation of gene expression. We use DNA tumor viruses and the response of cells to these viruses to probe the changes that normal cells undergo in the process of becoming cancer cells. These issues are addressed through a coordinated, multidisciplinary program of research in the fields of genetics, moleculare and cell biology, and biochemistry. The program is closely integrated, consisting of nine interrelated research Projects, which are distributed among seven Project Leader, and three Core Components, which promotes the research activities conducted in the scientific Projects.